Molecular,Cellular and Functional Changes in the Retinas of Young Adult Mice Lacking the Voltage-Gated K+ Channel Subunits Kv8.2 and K2.1

Cone Dystrophy with Supernormal Rod Response (CDSRR) is a rare autosomal recessive disorder leading to severe visual impairment in humans, but little is known about its unique pathophysiology. We have previously shown that CDSRR is caused by mutations in the KCNV2 (Potassium Voltage-Gated Channel Modifier Subfamily V Member 2) gene encoding the Kv8.2 subunit, a modulatory subunit of voltage-gated potassium (Kv) channels. In a recent study, we validated a novel mouse model of Kv8.2 deficiency at a late stage of the disease and showed that it replicates the human electroretinogram (ERG) phenotype. In this current study, we focused our investigation on young adult retinas to look for early markers of disease and evaluate their effect on retinal morphology, electrophysiology and immune response in both the Kv8.2 knockout (KO) mouse and in the Kv2.1 KO mouse, the obligate partner of Kv8.2 in functional retinal Kv channels. By evaluating the severity of retinal dystrophy in these KO models, we demonstrated that retinas of Kv KO mice have significantly higher apoptotic cells, a thinner outer nuclear cell layer and increased activated microglia cells in the subretinal space. Our results indicate that in the murine retina, the loss of Kv8.2 subunits contributes to early cellular and physiological changes leading to retinal dysfunction. These results could have potential implications in the early management of CDSRR despite its relatively nonprogressive nature in humans.     

Analysis of a number and type of publications that editors publish in their own journals: case study of scholarly journals in Croatia

To assess the publication practices of editors in their own journals, we analysed the number of articles that Croatian editors published in the journals they edit. From 2005 to 2008, 256 decision-making editors of 180 journals published a total of 887 publications in their own journals. Out of these, 332 were relevant for their academic promotion. Only 18 editors published 5 or more articles in their own journals. A single journal had regulations for self-publishing in the instructions for authors. Although the majority of editors did not misuse their own journals for scientific publishing and academic promotion, there is a need for greater transparency of the declaration and management of editorial conflict of interest in academic and scholarly journals.     

Bounds on transient phase plastic deformations in optimal design of steel frames subjected to cyclic loads

A minimum volume multicriterion design of elastic perfectly plastic steel frames subjected to a combination of quasi-static fixed and cyclic loads, bounding the transient phase plastic deformations, is proposed. The problem is formulated according to a plastic shakedown criterion, so that incremental and instantaneous collapse are certainly prevented when the frame is subjected to very strongly amplified cyclic loads. The further condition that the structure must also behave elastically in serviceability conditions is imposed. Since the steady-state loading history is known it is possible to directly bound the steady-state plastic deformations. By applying a suitable own bounding theorem, it is also possible to indirectly bound the transient plastic deformations, whichever the unknown transient real loading history is. A numerical application confirms the fundamental role played by the transient phase plastic deformations both on the design as well as on the structural behaviour and the great performance of the proposed formulation.     

Nanostructural depth-profile and field-effect properties of poly(alkoxyphenylene-thienylene) Langmuir-Schäfer thin-films

The correlations between morphological features and field-effect properties of poly(alkoxyphenylene-thiophene) thin Langmuir-Schäfer film deposited on differently terminated gate dielectric surfaces, namely bare and methyl functionalized thermal silicon dioxide (t-SiO₂), have been systematically studied. The film morphology has been investigated at different film thickness by Scanning Force Microscopy. Films thicker than a few layers show comparable morphology on both dielectric surfaces while differences are seen for the ultra-thin polymer deposit in close proximity to the substrate. Such deposit is notably more heterogeneous on bare t-SiO₂, while a more compact and uniform nanogranular structure is observed on the silylated t-SiO₂. As to the field-effect properties, the methyl-terminated gate dielectric surface leads to a two order of magnitude mobility enhancement along with a field-effect thickness independent conductance.     

Consumption of Fish in Chronic Kidney Disease – A Matter of Depth

Fish is an excellent source of ω-3 polyunsaturated fatty acids (PUFAs), amino acids, collagen, vitamins, and iodine and its intake is associated with health benefits, mainly reduces risk of cardiovascular mortality. However, recent studies have shown that fish is also an important source of trimethylamine N-oxide (TMAO), a uremic toxin produced by the gut microbiota that promotes an increased risk of cardiovascular diseases. In patients with chronic kidney disease (CKD), TMAO levels are markedly increased due to gut dysbiosis and reduced kidney function. No study has yet evaluated the effects of a fish-rich diet on TMAO plasma levels and cardiovascular outcomes. This review discusses the pros and cons of a fish-rich diet in patients with CKD – a matter of depth.     

Treatment with the Bacterial Toxin CNF1 Selectively Rescues Cognitive and Brain Mitochondrial Deficits in a Female Mouse Model of Rett Syndrome Carrying a MeCP2-Null Mutation

Rett syndrome (RTT) is a rare neurological disorder caused by mutations in the X-linked MECP2 gene and a major cause of intellectual disability in females. No cure exists for RTT. We previously reported that the behavioural phenotype and brain mitochondria dysfunction are widely rescued by a single intracerebroventricular injection of the bacterial toxin CNF1 in a RTT mouse model carrying a truncating mutation of the MeCP2 gene (MeCP2-308 mice). Given the heterogeneity of MECP2 mutations in RTT patients, we tested the CNF1 therapeutic efficacy in a mouse model carrying a null mutation (MeCP2-Bird mice). CNF1 selectively rescued cognitive defects, without improving other RTT-related behavioural alterations, and restored brain mitochondrial respiratory chain complex activity in MeCP2-Bird mice. To shed light on the molecular mechanisms underlying the differential CNF1 effects on the behavioural phenotype, we compared treatment effects on relevant signalling cascades in the brain of the two RTT models. CNF1 provided a significant boost of the mTOR activation in MeCP2-308 hippocampus, which was not observed in the MeCP2-Bird model, possibly explaining the differential effects of CNF1. These results demonstrate that CNF1 efficacy depends on the mutation beared by MeCP2-mutated mice, stressing the need of testing potential therapeutic approaches across RTT models.     

Molecular Pathogenesis and Treatment Perspectives for Hypereosinophilia and Hypereosinophilic Syndromes

Hypereosinophilia (HE) is a heterogeneous condition with a persistent elevated eosinophil count of >350/mm³, which is reported in various (inflammatory, allergic, infectious, or neoplastic) diseases with distinct pathophysiological pathways. HE may be associated with tissue or organ damage and, in this case, the disorder is classified as hypereosinophilic syndrome (HES). Different studies have allowed for the discovery of two major pathogenetic variants known as myeloid or lymphocytic HES. With the advent of molecular genetic analyses, such as T-cell receptor gene rearrangement assays and Next Generation Sequencing, it is possible to better characterize these syndromes and establish which patients will benefit from pharmacological targeted therapy. In this review, we highlight the molecular alterations that are involved in the pathogenesis of eosinophil disorders and revise possible therapeutic approaches, either implemented in clinical practice or currently under investigation in clinical trials.     

Transformation on Infinite Double Series and Applications to Harmonic Number Identities

A general transformation formula between an infinite double series and an infinite single sum is established, which specializes to several infinite double series identities, including a recent one due to Lyons, Paule and Riese (2002).